Outcomes of retropupillary iris claw lens implantation in patients with intraocular lens dislocation and low (less than 1000 cells/mm2) corneal endothelial cell density.

BACKGROUND: Posterior chamber intraocular lens (IOL) dislocation is a common complication of cataract surgery. Dislocated IOLs often require surgical intervention due to the potentially severe risks of leaving this condition untreated. If a patient with extremely low corneal endothelial cell density (ECD) presents with IOL dislocation, the surgeon faces a crucial dilemma of choosing the most optimal surgical treatment option. We sought to investigate the efficacy and safety of retropupillary iris claw intraocular lens (R-IOL) implantation in patients with IOL dislocation and extremely low (< 1000 cells/mm2) ECD. METHODS: We retrospectively reviewed the medical records of nine patients (all men) whose pre-operative ECD was < 1000 cells/mm2 and who underwent R-IOL implantation due to intraocular subluxation or total dislocation into the vitreous cavity between 2014 and 2020. We evaluated corneal endothelial function and visual outcomes after surgery. RESULTS: Nine patients were included in this study. The mean age at diagnosis was 64.89 ± 7.15 years (range 57-76 years), and the follow-up duration was 37.93 ± 23.72 months (range 18.07-89.07 months). No patients developed bullous keratopathy during follow-up. Compared to the initial ECD, corneal thickness (CT), coefficient variation of cell area (CV) and percentage of hexagonal cells (HEX), there was no statistically significant decrease in the ECD, CV, and HEX at last follow-up (P = 0.944, 0.778, 0.445, 0.443). There was significant improvement in the mean uncorrected distance visual acuity (UDVA) at the last follow-up (average 0.13 logMAR, 20/27 Snellen) compared to the pre-operative mean UDVA (average 1.09 logMAR, 20/250 Snellen) (P < 0.01). CONCLUSIONS: R-IOL implantation did not result in a statistically significant decline in corneal endothelial function in patients with preoperatively low ECD, and it significantly improved the mean UDVA postoperatively. R-IOL implantation appears to be a safe and effective treatment modality for intraocular lens dislocation in patients with low ECD (< 1000 cells/mm²); however, long-term follow-up studies are warranted to corroborate these findings.

Circulating miRNA-4701-3p as a predictive biomarker of cardiovascular disease which induces angiogenesis by inhibition of TOB2.

Angiogenesis is mainly regulated by the delivery of VEGF-dependent signaling to cells. However, the angiogenesis mechanism regulated by VEGF-induced miRNA is still not understood. After VEGF treatment in HUVECs, we screened the changed miRNAs through small-RNA sequencing and found VEGF-induced miR-4701-3p. Furthermore, the GFP reporter gene was used to reveal that TOB2 expression was regulated by miR-4701-3p, and it was found that TOB2 and miR-4701-3p modulation could cause angiogenesis in an in-vitro angiogenic assay. Through the luciferase assay, it was confirmed that the activation of the angiogenic transcription factor MEF2 was regulated by the suppression and overexpression of TOB2 and miR-4701-3p. As a result, MEF2 downstream gene mRNAs that induce angiogenic function were regulated. We used the NCBI GEO datasets to reveal that the expression of TOB2 and MEF2 was significantly changed in cardiovascular disease. Finally, it was confirmed that the expression of circulating miR-4701-3p in the blood of myocardial infarction patients was remarkably increased. In patients with myocardial infarction, circulating miR-4701-3p was increased regardless of age, BMI, and sex, and showed high AUC levels in specificity and sensitivity analysis (AUROC) (AUC = 0.8451, 95 % CI 0.78-0.90). Our data showed TOB2-mediated modulation of MEF2 and its angiogenesis by VEGF-induced miR-4701-3p in vascular endothelial cells. In addition, through bioinformatics analysis using GEO data, changes in TOB2 and MEF2 were revealed in cardiovascular disease. We suggest that circulating miR-4701-3p has high potential as a biomarker for myocardial infarction.

Immune signature and therapeutic approach of natural killer cell in chronic liver disease and hepatocellular carcinoma.

Natural killer (NK) cells are one of the key members of innate immunity that predominantly reside in the liver, potentiating immune responses against viral infections or malignant tumors. It has been reported that changes in cell numbers and function of NK cells are associated with the development and progression of chronic liver diseases (CLDs) including non-alcoholic fatty liver disease, alcoholic liver disease, and chronic viral hepatitis. Also, it is known that the crosstalk between NK cells and hepatic stellate cells plays an important role in liver fibrosis and cirrhosis. In particular, the impaired functions of NK cells observed in CLDs consequently contribute to occurrence and progression of hepatocellular carcinoma (HCC). Chronic infections by hepatitis B or C viruses counteract the anti-tumor immunity of the host by producing the sheddases. Soluble major histocompatibility complex class I polypeptide-related sequence A (sMICA), released from the cell surfaces by sheddases, disrupts the interaction and affects the function of NK cells. Recently, the MICA/B-NK stimulatory receptor NK group 2 member D (NKG2D) axis has been extensively studied in HCC. HCC patients with low membrane-bound MICA or high sMICA concentration have been associated with poor prognosis. Therefore, reversing the sMICA-mediated downregulation of NKG2D has been proposed as an attractive strategy to enhance both innate and adaptive immune responses against HCC. This review aims to summarize recent studies on NK cell immune signatures and its roles in CLD and hepatocellular carcinogenesis and discusses the therapeutic approaches of MICA/B-NKG2D-based or NK cell-based immunotherapy for HCC.

Yeast-derived particulate beta-glucan induced angiogenesis via regulating PI3K/Src and ERK1/2 signaling pathway.

The importance of ß-glucan from S. cerevisiae in angiogenesis has not been well studied. We investigated whether ß-glucan induces angiogenesis through PI3K/Src and ERK1/2 signaling pathway in HUVECs. We identified that ß-glucan induced phosphorylation of PI3K, Src, Akt, eNOS, and ERK1/2. Subsequently, we found that this phosphorylation increased the viability of HUVECs. We also observed that stimulation of ß-glucan promoted the activity of MEF2 and MEF2-dependent pro-angiogenic genes, including EGR2, EGR3, KLF2, and KLF4. Additionally, the role of ß-glucan in angiogenesis was confirmed using in vitro and ex vivo experiments including cell migration, capillary-like tube formation and mouse aorta ring assays. To determine the effect of ß-glucan on the PI3K/Akt/eNOS and ERK1/2 signaling pathway, PI3K inhibitor wortmannin and ERK1/2 inhibitor SCH772984 were used. Through the Matrigel plug assay, we confirmed that ß-glucan significantly increased angiogenesis in vivo. Taken together, our study demonstrates that ß-glucan promotes angiogenesis via through PI3K and ERK1/2 signaling pathway.

Ticagrelor, but Not Clopidogrel, Attenuates Hepatic Steatosis in a Model of Metabolic Dysfunction-Associated Steatotic Liver Disease.

BACKGROUND: Previous studies have suggested that platelets are associated with inflammation and steatosis and may play an important role in liver health. Therefore, we evaluated whether antiplatelet agents can improve metabolic disorder-related fatty liver disease (MASLD). METHODS: The mice used in the study were fed a high-fat-diet (HFD) and were stratified through liver biopsy at 18 weeks. A total of 22 mice with NAFLD activity scores (NAS) ≥ 4 were randomly divided into three groups (HFD-only, clopidogrel (CLO; 35 mg/kg/day), ticagrelor (TIC; 40 mg/kg/day) group). And then, they were fed a feed mixed with the respective drug for 15 weeks. Blood and tissue samples were collected and used in the study. RESULTS: The TIC group showed a significantly lower degree of NAS and steatosis than the HFD group (p = 0.0047), but no effect on the CLO group was observed. Hepatic lipogenesis markers' (SREBP1c, FAS, SCD1, and DGAT2) expression and endoplasmic reticulum (ER) stress markers (CHOP, Xbp1, and GRP78) only reduced significantly in the TIC treatment group. Inflammation genes (MCP1 and TNF-α) also decreased significantly in the TIC group, but not in the CLO group. Nile red staining intensity and hepatic lipogenesis markers were reduced significantly in HepG2 cells following TIC treatment. CONCLUSION: Ticagrelor attenuated NAS and hepatic steatosis in a MASLD mice model by attenuating lipogenesis and inflammation, but not in the CLO group.

Changes in Intraocular Pressure and Anterior Chamber Parameters Following Cataract Surgery, Vitrectomy, and Combined Surgery.

PURPOSE: The aim of this study is to investigate changes in intraocular pressure (IOP) and anterior-segment parameters before and after cataract surgery, vitrectomy, and combined surgery. METHODS: The records of patients who had undergone cataract surgery (cataract group), vitrectomy (vitrectomy group), or combined cataract surgery and vitrectomy (combined group) at our hospital were retrospectively examined. The vitrectomy group consisted of pseudophakic eyes. IOP and anterior-segment measurements, including anterior chamber depth (ACD), angle opening distance (AOD), trabecular-iris angle (TIA), and trabecular-iris space area (TISA), were measured using swept-source anterior-segment optical coherence tomography before and 6 months after surgery in 41, 15, and 40 eyes, respectively. RESULTS: In the cataract and combined groups, there was a decrease in IOP (cataract group: from 15.8 to 13.4 mmHg, p <0.001; combined group: from 15.8 to 14.2 mmHg, p = 0.002) and an increase in the central corneal thickness after surgery (p <0.001). The ACD increased in all groups, with a smaller increase in the vitrectomy group (p <0.03). Postoperative AOD, TIA, and TISA were significantly increased in the cataract and combined groups (p <0.02). Higher preoperative IOP and larger IOP reduction after surgery were correlated with smaller preoperative AOD, TISA, and TIA in cataract and combined groups (p <0.034). A small preoperative ACD was related to smaller preoperative AOD, TISA, TIA (r > 0.649, p <0.001), and postoperative IOP reduction in the cataract and combined groups (r = 0.377, p = 0.018 and r = 0.559, p = 0.001, respectively). CONCLUSIONS: Compared to the vitrectomy group, the cataract and combined groups showed reduced postoperative IOP and increased AOD, TISA, and TIA. In these two groups, patients with shallower preoperative ACDs showed greater changes in IOP after surgery. Changes in IOP after surgery are thought to be related to changes in the anterior segment caused by the removal of the crystalline lens.

HDAC5-mediated exosomal Maspin and miR-151a-3p as biomarkers for enhancing radiation treatment sensitivity in hepatocellular carcinoma.

BACKGROUND: Tumor-derived exosomes are critical elements of the cell-cell communication response to various stimuli. This study aims to reveal that the histone deacetylase 5 (HDAC5) and p53 interaction upon radiation in hepatocellular carcinoma intricately regulates the secretion and composition of exosomes. METHODS: We observed that HDAC5 and p53 expression were significantly increased by 2 Gy and 4 Gy radiation exposure in HCC. Normal- and radiation-derived exosomes released by HepG2 were purified to investigate the exosomal components. RESULTS: We found that in the radiation-derived exosome, exosomal Maspin was notably increased. Maspin is known as an anti-angiogenic gene. The expression of Maspin was regulated at the cellular level by HDAC5, and it was elaborately regulated and released in the exosome. Radiation-derived exosome treatment caused significant inhibition of angiogenesis in HUVECs and mouse aortic tissues. Meanwhile, we confirmed that miR-151a-3p was significantly reduced in the radiation-derived exosome through exosomal miRNA sequencing, and three HCC-specific exosomal miRNAs were also decreased. In particular, miR-151a-3p induced an anti-apoptotic response by inhibiting p53, and it was shown to induce EMT and promote tumor growth by regulating p53-related tumor progression genes. In the HCC xenograft model, radiation-induced exosome injection significantly reduced angiogenesis and tumor size. CONCLUSIONS: Our present findings demonstrated HDAC5 is a vital gene of the p53-mediated release of exosomes resulting in tumor suppression through anti-cancer exosomal components in response to radiation. Finally, we highlight the important role of exosomal Maspin and mi-151a-3p as a biomarker in enhancing radiation treatment sensitivity. Therapeutic potential of HDAC5 through p53-mediated exosome modulation in radiation treatment of hepatocellular carcinoma.

Novel Inhibitor of Mixed-Lineage Kinase Domain-Like Protein: The Antifibrotic Effects of a Necroptosis Antagonist.

The pseudokinase mixed-lineage kinase domain-like protein plays a crucial role in programmed cell death via necroptosis. We developed a novel mixed-lineage kinase domain-like inhibitor, P28, which demonstrated potent necroptosis inhibition and antifibrotic effects. P28 treatment directly inhibited mixed-lineage kinase domain-like phosphorylation and oligomerization after necroptosis induction, inhibited immune cell death after necroptosis, and reduced the expression of adhesion molecules. Additionally, P28 treatment reduced the level of activation of hepatic stellate cells and the expression of hepatic fibrosis markers induced by necroptosis stimulation. Unlike the necrosulfonamide treatment, the P28 treatment did not induce cytotoxicity. Finally, the cysteine covalent bonding of P28 was confirmed by liquid chromatography-tandem mass spectrometry.

Human primary myoblasts derived from paraspinal muscle reflect donor age as an experimental model of sarcopenia.

BACKGROUND: Low back pain is a general phenomenon of aging, and surgery is an unavoidable choice to relieve severe back pain. The discarded surgical site during surgery is of high value for muscle and muscle-related research. This study investigated the age-dependent properties of patients' paraspinal muscles at the cellular level. METHODS: To define an association of paraspinal muscle degeneration with sarcopenia, we analyzed lumbar paraspinal muscle and myoblasts isolated from donors of various ages (25-77 years). Preoperative evaluations were performed by bioimpedance analysis using the InBody 720, magnetic resonance (MR) imaging of the lumbar spine, and lumbar extension strength using a lumbar extension dynamometer. In addition, the growth and differentiation capacity of myoblasts obtained from the donor was determined using proliferation assay and western blotting. RESULTS: The cross-sectional area of the lumbar paraspinal muscle decreased with age and was also correlated with the appendicular skeletal muscle index (ASM/height2). Human primary myoblasts isolated from paraspinal muscle preserved their proliferative capacity in vitro, which tended to decrease with donor age. The age-dependent decline in myoblast proliferation was correlated with levels of cell cycle inhibitory proteins (p16INK4a, p21CIP1, and p27KIP1) associated with cellular senescence. Primary myoblasts isolated from younger donors differentiated into multinucleate myotubes earlier and at a higher rate than those from older donors in vitro. Age-dependent decline in myogenic potential of the isolated primary myoblasts was likely correlated with the inactivation of myogenic transcription factors such as MyoD, myogenin, and MEF2c. CONCLUSIONS: Myoblasts isolated from human paraspinal muscle preserve myogenic potential that correlates with donor age, providing an in vitro model of sarcopenia.

Clinical Features, Long-Term Outcomes, and Prognostic Factors of Eales' Disease in Korean Patients.

PURPOSE: We studied Korean patients with Eales' disease to document clinical features, long-term outcomes, and explore its association with TB, given South Korea's high TB burden. METHODS: We retrospectively reviewed medical records of Eales' disease patients for clinical characteristics, long-term outcomes, and its association with TB. RESULTS: Among 106 eyes, the average age of diagnosis was 39.28 years, with 82.7% male and 58.7% having unilateral involvement. Patients who underwent vitrectomy showed greater long-term improvement in visual acuity (P = .047), while those with glaucoma filtration surgery showed less improvement (P = .008). Having glaucoma through disease progression was associated with poor visual outcomes (odds ratio=15.556, P < .02). 27 out of 39 patients (69.23%) who underwent IGRA screening tested positive for TB. CONCLUSIONS: In Korean patients with Eales' disease, we observed male predominance, unilateral presentation, older age of onset, and a link with TB. Timely diagnosis and management should be considered to maintain good vision in patients with Eales' disease.

A Novel Method for Transillumination.

PURPOSE: To introduce a cost-efficient device for transillumination in the management of uveal melanoma. METHODS: Todorich Illuminated Depressor is a ball-point depressor, designed to work with the 23-, 25- and 27-gauge Alcon Constellation endoillumination. It was invented to allow indentation and peripheral vitreous visualization for vitrectomy. RESULTS: Todorich depressor combined with endoillumination can also work as a device for transillumination for tumor localization. We started using this method of transillumination for the management of uveal melanomas since September 2020 and have successfully performed Ru-106 plaque brachytherapy for 10 cases of uveal melanoma. Three were large choroidal melanoma cases, and en bloc tumor resection by partial lamellar sclerouvectomy was successfully performed after precise localization of tumors using this method. CONCLUSION: Alcon Constellation endoillumination capped with Todorich Illuminated Depressor is an affordable and viable alternative for transillumination of intraocular tumors.

Angiogenic adipokine C1q-TNF-related protein 9 ameliorates myocardial infarction via histone deacetylase 7-mediated MEF2 activation.

C1q/tumor necrosis factor-related protein 9 (CTRP9) is an adipokine and has high potential as a therapeutic target. However, the role of CTRP9 in cardiovascular disease pathogenesis remains unclear. We found CTRP9 to induce HDAC7 and p38 MAPK phosphorylation via tight regulation of AMPK in vascular endothelial cells, leading to angiogenesis through increased MEF2 activity. The expression of CTRP9 and atheroprotective MEF2 was decreased in plaque tissue of atherosclerotic patients and the ventricle of post-infarction mice. CTRP9 treatment inhibited the formation of atherosclerotic plaques in ApoE KO and CTRP9 KO mice. In addition, CTRP9 induced significant ischemic injury prevention in the post-MI mice. Clinically, serum CTRP9 levels were reduced in patients with MI compared with healthy controls. In summary, CTRP9 induces a vasoprotective response via the AMPK/HDAC7/p38 MAPK pathway in vascular endothelial cells, whereas its absence can contribute to atherosclerosis and MI. Hence, CTRP9 may represent a valuable therapeutic target and biomarker in cardiovascular diseases.

5-Fluorouracil-Immobilized Hyaluronic Acid Hydrogel Arrays on an Electrospun Bilayer Membrane as a Drug Patch.

The hyaluronic acid (HA) hydrogel array was employed for immobilization of 5-fluorouracil (5-FU), and the electrospun bilayer (hydrophilic: polyurethane/pluronic F-127 and hydrophobic: polyurethane) membrane was used to support the HA hydrogel array as a patch. To visualize the drug propagating phenomenon into tissues, we experimentally investigated how FITC-BSA diffused into the tissue by applying hydrogel patches to porcine tissue samples. The diffusive phenomenon basically depends on the FITC-BSA diffusion coefficient in the hydrogel, and the degree of diffusion of FITC-BSA may be affected by the concentration of HA hydrogel, which demonstrates that the high density of HA hydrogel inhibits the diffusive FITC-BSA migration toward the low concentration region. YD-10B cells were employed to investigate the release of 5-FU from the HA array on the bilayer membrane. In the control group, YD-10B cell viability was over 98% after 3 days. However, in the 5-FU-immobilized HA hydrogel array, most of the YD-10B cells were not attached to the bilayer membrane used as a scaffold. These results suggest that 5-FU was locally released and initiated the death of the YD-10B cells. Our results show that 5-FU immobilized on HA arrays significantly reduces YD-10B cell adhesion and proliferation, affecting cells even early in the cell culture. Our results suggest that when 5-FU is immobilized in the HA hydrogel array on the bilayer membrane as a drug patch, it is possible to control the drug concentration, to release it continuously, and that the patch can be applied locally to the targeted tumor site and administer the drug in a time-stable manner. Therefore, the developed bilayer membrane-based HA hydrogel array patch can be considered for sustained release of the drug in biomedical applications.

Clinical and Multimodal Imaging Features of Choroidal Nevi in the Korean Population.

Choroidal nevus is a precursor of choroidal melanoma. Multimodal imaging has become vital in predicting the malignant transformation of choroidal nevi. This single-center, retrospective study analyzed clinical characteristics and multimodal imaging findings of 168 choroidal nevi (164 patients) of the Korean population. The mean age at presentation was 50 ± 15 (range, 13−85) (women, n = 88 [53.7%]). Choroidal nevi (melanotic, n = 164 [97.6%]; postequatorial, n = 160 [95.2%]) were densely located between the optic disc and foveola (65.5%). The mean maximum linear basal diameter on fundus photography and thickness on optical coherence tomography were 2.97 ± 1.51 mm and 521 ± 297 µm, respectively. On ultrasonography, the mean thickness was 0.87 ± 0.60 mm. Choroidal nevi in women were associated with a higher maximum linear basal diameter (3.23 ± 1.65 vs. 2.68 ± 1.21 mm; p = 0.033) and age at diagnosis (52 ± 14 vs. 47 ± 16 years; p = 0.046) than those in men. Choroidal nevi with associated subretinal fluid (23.2%) presented with larger basal diameter (p = 0.049) and thickness on B-scan and optical coherence tomography (p < 0.001), but a younger age at diagnosis (p < 0.001) than those of dry nevi. This multimodal imaging study of choroidal nevi revealed some distinct characteristics, including topographic distribution, sex-related differences, and a younger age at diagnosis of nevi with fluid.

Pattern Analysis of Laser Fiber Degradation According to the Laser Setting: In Vitro Study of the Double-Firing Phenomenon.

BACKGROUND: It is essential to understand the mechanism of the various causes of laser fiber damage and an ideal method of reducing endoscope damage induced by laser emission in multiple sites. This study classified the different patterns of laser fiber degradation according to laser settings and analyzed the role of cavitation bubbles to find a desirable way of minimizing endoscope damage. METHODS: A total of 118 laser fibers were analyzed after 1-,3-, and 5-min laser emission to artificial stones under the settings of 1 J-10 Hz, 1 J-20 Hz, 1 J-30 Hz, and 2 J-10 Hz. Every 3 cm from the fiber tip was marked and examined with a digital microscope and a high-speed camera. The images of the fibers and the movement of cavitation bubbles were taken with a distance of 1 to 5 mm from the gel. RESULTS: Seven types of fiber damage (charring, limited and extensive peeled-off, bumpy, whitish plaque, crack, and break-off) coincided during laser emission. Damages rapidly increased with emission time > 3 minutes regardless of the laser settings. The damaged lengths covered 5 mm on average, and the fibers at 5-min emission were significantly shorter than others. The fiber durability of 1J-10Hz setting was better than other settings after 3-min laser emission. Backward movement of the cavitation bubbles was found at the 1-mm distance from the gel, and the damaged lengths were longer than the diameters of the cavitation bubbles because of their proximal movement. CONCLUSION: The damage patterns of the laser fiber tips were classified into seven types. The heat damage around the surface of the laser fiber can be increased according to the high-energy or high-frequency laser setting, a short distance to the stone, a short distance from the tips of flexible ureteroscopes, no cutting laser fiber procedures, and the inappropriate use of irrigation fluid or laser fiber jacket.

High Iron Exposure from the Fetal Stage to Adulthood in Mice Alters Lipid Metabolism.

Iron supplementation is recommended during pregnancy and fetal growth. However, excess iron exposure may increase the risk of abnormal fetal development. We investigated the potential side effects of high iron levels in fetuses and through their adult life. C57BL/6J pregnant mice from 2 weeks of gestation and their offspring until 30 weeks were fed a control (CTRL, FeSO4 0 g/1 kg) or high iron (HFe, FeSO4 9.9 g/1 kg) diets. HFe group showed higher iron accumulation in the liver with increased hepcidin, reduced TfR1/2 mRNAs, and lowered ferritin heavy chain (FTH) proteins in both liver and adipose tissues despite iron loading. HFe decreased body weight, fat weight, adipocyte size, and triglyceride levels in the blood and fat, along with downregulation of lipogenesis genes, including PPARγ, C/EBPα, SREBP1c, FASN, and SCD1, and fatty acid uptake and oxidation genes, such as CD36 and PPARα. UCP2, adiponectin, and mRNA levels of antioxidant genes such as GPX4, HO-1, and NQO1 were increased in the HFe group, while total glutathione was reduced. We conclude that prolonged exposure to high iron from the fetal stage to adulthood may decrease fat accumulation by altering ferritin expression, adipocyte differentiation, and triglyceride metabolism, resulting in an alteration in normal growth.

Discovery of dipeptidyl peptidase-4 inhibitor specific biomarker in non-alcoholic fatty liver disease mouse models using modified basket trial.

BACKGROUND/AIMS: We aimed to define an optimal target population and drug-specific biomarkers that may predict dipeptidyl peptidase (DPP)-4 inhibitor responses in non-alcoholic fatty liver disease (NAFLD). METHODS: An exploration study (study I) was performed using three different NAFLD models (basket study design; high-fat diet [HFD], methionine choline-deficient diet [MCD], and high-cholesterol Western diet [WD] models). RNA transcriptome analysis was performed on pre-studied liver tissues to identify biomarkers that could predict the response to DPP-4 inhibitors. In the validation study (study II), the HFD-induced NAFLD model was divided into high and low hepatic insulin-like growth factor binding protein 1 (Igfbp-1) groups based on the pre-study liver biopsy. RESULTS: DPP-4 inhibitor attenuated the NAFLD activity score and fibrosis stage in the HFD model but not in the WD and MCD models. The overall response rate was 19% across the modified basket NAFLD trial and 42%, 25%, and 0% in the HFD, WD, and MCD models. Hepatic Igfbp-1 expression was higher in the responder group than in the non-responder group in pre-study biopsy samples. In contrast, hepatic Igfbp-1 expression was lower in the responder group than in the non-responder group in the end-study biopsy samples. DPP-4 inhibitor response rates were 83% and 17% in the baseline hepatic high Igfbp-1 and low Igfbp-1 groups, respectively. Hepatic messenger RNA Igfbp-1 expression was positively correlated with serum IGFBP-1 levels. CONCLUSION: The DPP-4 inhibitor response was higher in the HFD phenotype and pre-treatment levels of hepatic or serum IGFBP-1 were high.

Retropupillary Iris Fixation of an Artisan Myopia Lens for Intraocular Lens Dislocation and Aphakia in Eyes with Extremely High Myopia: A Case Series and a Literature Review.

INTRODUCTION: To describe the outcomes of retropupillary iris fixation of an iris claw Artisan Myopia intraocular lens (IOL), and to review literature on retropupillary iris fixation of iris claw models for myopia for the correction of aphakia and IOL dislocation in eyes with extremely high myopia. METHODS: Single-center, retrospective case series. Three patients (three eyes) with pathological myopia underwent retropupillary iris fixation of the iris claw Artisan Myopia model 204 for the correction of aphakia and IOL dislocation. After IOL power calculation, we found that the Artisan Aphakia IOL was not available for these patients. One patient had a history of previous extracapsular cataract extraction and two patients exhibited IOL-bag complex dislocation. The target lens power was calculated using ultrasound biometry and the Sanders-Retzlaff-Kraff theoretical and T2 formulae, with an A-constant of 103.8. All surgeries were performed by a single surgeon. Visual outcomes were assessed at 12-48 months after surgery. RESULTS: The mean axial length was 34.33 ± 0.21 mm. The power of the implanted Artisan IOLs ranged between - 4.00 and - 3.00 diopter. The corrected distance visual acuity, measured in logarithm of the minimum angle of resolution units, improved after surgery in all eyes, from 0.60 ± 0.36 logMAR before surgery to 0.40 ± 0.43 logMAR after surgery at 12 months postoperatively and remained stationary thereafter. There were no postoperative complications. CONCLUSIONS: Retropupillary iris fixation of Artisan Myopia IOLs may be a safe and effective surgical treatment option for the correction of aphakia and IOL dislocation in patients with extremely high myopia.

The Effect of Omega-3 Enriched Oral Nutrition Supplement on Nutritional Indices and Quality of Life in Gastrointestinal Cancer Patients: A Randomized Clinical Trial.

OBJECTIVE: Gastrointestinal (GI) cancer patients often experience severe malnutrition during cancer therapies due to gastrointestinal dysfunctions including poor digestion and absorption as well as tumor-associated anorexia. In this study, we performed a randomized clinical trial to determine the efficacy of oral nutrition supplement (ONS) enriched with omega-3 fatty acids on nutritional status, quality of life (QOL), and pro-inflammatory indices. METHODS: Patients diagnosed with GI cancers were recruited and screened for eligibility. A total of 58 patients were randomly allocated to either the control group (n=27) or the experimental group (n=31). The intervention group received 200 ml ONS twice a day while the control group received routine care. Anthropometrics, Patient-Generated Subjective Global Assessment (PG-SGA) score, QOL score and nutrient intake data were collected at baseline, week 4 and week 8. Blood was drawn for biochemical assessments. Nine patients from each group dropped out of the study Forty patients (18 control patients and 22 intervention patients) completed the study. RESULTS: This study showed that ONS intervention improved PG-SGA scores in the intervention group (p<0.01). Scores of physical functioning score and role functioning were declined only in the control group and the difference between week 8 and baseline for role functioning was significant (p<0.001). Fatigue score was steadily decreased in the experiment group, and the differences between week 8 and baseline was significant between two groups (p<0.02). However, no statistically significant improvement in biochemical markers of nutritional status and pro-inflammatory cytokine concentrations were found. These results suggests that ONS intervention for 8 weeks improves PG-SGA scores and QOL scores in patients undergoing cancer therapy.